Ca2+-induced Ca2+ release in cardiac and smooth muscle cells.

Abstract

Ca(2+) influx across plasma membranes may trigger Ca(2+) release by activating ryanodine-sensitive receptors in the sarcoplasmic reticulum. This process is called Ca(2+)-induced Ca(2+) release, and may be important in regulating cytosolic Ca(2+) concentration ([Ca(2+)](i)). In cardiac cells, the initial [Ca(2+)](i) increase, caused by L-type Ca(2+) current, is profoundly amplified with Ca(2+) release. The synchronized opening of several ryanodine-sensitive Ca(2+)-releasing channels was detected as discreet and highly localized Ca(2+) elevation, and termed as a 'Ca(2+) spark'. A Ca(2+) spark is under local control of an L-type Ca(2+) channel, and therefore a Ca(2+) spark does not normally trigger subsequent Ca(2+) sparks in the neighbouring area. In smooth muscle cells, the importance of Ca(2+)-induced Ca(2+) release in elevating [Ca(2+)](i) appears to differ among preparations and species. Significant elevation in [Ca(2+)](i) during depolarization was attributed to Ca(2+) release in some smooth muscle cells, but not in others. Ca(2+) sparks are also identified in smooth muscle cells, and may play a role as functional elementary events for Ca(2+)-induced Ca(2+) release. At rest, Ca(2+) sparks may be also important in regulating smooth muscle membrane potential. Ca(2+) sparks occurring at rest do not raise global [Ca(2+)](i), but trigger spontaneous transient outward currents (STOCs) or spontaneous transient inward currents (STICs), the former producing hyperpolarization; the latter, depolarization. Thus there may be multiple facets for Ca(2+)-induced Ca(2+) release in regulating the contractile status of smooth muscle cells.